Ame-miR-1-3p of bee venom reduced cell viability through the AZIN1/OAZ1-ODC1-polyamines pathway and enhanced the defense ability of honeybee (Apis mellifera L.).

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.

Development and preliminary application of a quadruplex real-time PCR assay for differential detection of porcine circovirus 1-4 in Chengdu, China.

Porcine circovirus (PCV) typically causes severe immune suppression in pigs, leading to mixed clinical infections with various pathogens that can cause significant harm to the pig industry. PCV has four subgenotypes, with PCV4 being an emerging virus that requires investigation due to its potential for epidemic outbreaks. Therefore, there is a need to develop a method that can detect all four PCV strains simultaneously. In this study, four pairs of specific primers and TaqMan probes were designed based on the conserved sequence of the PCV1-4 ORF2 gene to establish a PCV1-4 TaqMan multiplex real-time quantitative PCR method. The novel method was compared to six commercial testing kits for its efficacy. Then, a total of 595 mixed samples of spleen and lymph node collected from 12 districts in Chengdu from July to December 2021 were tested using the novel method. The results showed that the novel PCV1-4 TaqMan multiplex real-time quantitative PCR detection method has satisfied specificity, sensitivity, and repeatability. The positive rates of PCV1, PCV2, and PCV3 in Chengdu were 2.18%, 31.60%, and 15.29%, respectively, while no positive PCV4 was detected. The mixed infection rate of PCV2 and PCV3 was 5.21%. Our novel method may be as a potential method for PCV1-4 detection. Currently, PCV2 is the main epidemic PCV subtype in Chengdu, while the potential threat of PCV4 should also be considered.

Modified Suture Button Latarjet Procedure With Coracoacromial Ligament And Pectoralis Minor Preservation Achieves Good Clinical Outcomes at 2-Year Follow-up: Case Series of Latarjet Technique.

PURPOSES: To evaluate if the modified suture button Latarjet procedure with coracoacromial ligament (CAL) and pectoralis minor (PM) preservation could achieve excellent outcomes at the 2-year follow-up. METHODS: During January 2019 to January 2021, data of patients who underwent the modified suture button Latarjet with CAL and PM preservation in our department was collected. The glenoid bone loss of these patients were above 20% or over 10% with high demands for exercise. Partial coracoid osteotomy was based on the results of the preoperative 3-dimensional computed tomography (3D CT) evaluation of the glenoid defect area (GDA) and corresponding coracoid process morphology. The preoperative and postoperative clinical results were assessed. The minimal clinically important difference (MCID) was utilized to compare improvement in clinical outcomes. Graft-glenoid union and remodeling were assessed using postoperative 3D CT, and magnetic resonance imaging (MRI) was performed to confirm the integrity of the CAL and PM postoperatively. RESULTS: 35 patients were included in this study; the mean follow-up time was 26.9 ± 1.9 months. No case of recurrent dislocation or sublaxity. Significant improvements were observed in mean visual analog scale (VAS) scores for pain during motion, American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and Walch-Duplay score (P < .001). The percentage of patients achieving at least an MCID improvement in clinical outcomes was: VAS 85.71%; ASES 97.14%; Rowe 100%; Walch-Duplay 97.14%. 33 patients (94.3% of all cases) were able to return to their preoperative sport levels, 34 grafts (97.1%) achieved bone union (1 soft union) in 6.3±2.2 months, and the coracoid grafts restored 97.1±4.0% of the perfect fitting circle (PFC) at the last follow-up. Postoperative CT scan showed that 31 grafts (88.6%) were placed ideally in vertical view. In the axial view, 25 grafts (82.9%) were flushed to the glenoid, whereas 1 and 5 grafts were fixed medially and laterally, respectively. The CAL and PM were visualized postoperatively. No arthropathy was observed in any patient at the last follow-up. CONCLUSIONS: The modified suture button Latarjet procedure with CAL and PM preservation obtained good clinical and radiological results without recurrence or complications. A substantial majority of patients (>85%) achieved the MCID for the VAS, ASES, ROWE, and Walch-Duplay scores. Additionally, the malpositioned graft (17.1%) did not cause arthropathy of the joints at 2-year follow-up.

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons.

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.

The clade III subfamily of OsSWEETs directly suppresses rice immunity by interacting with OsHMGB1 and OsHsp20L.

The clade III subfamily of OsSWEETs includes transmembrane proteins necessary for susceptibility to bacterial blight (BB). These genes are targeted by the specific transcription activator-like effector (TALE) of Xanthomonas oryzae pv. oryzae and mediate sucrose efflux for bacterial proliferation. However, the mechanism through which OsSWEETs regulate rice immunity has not been fully elucidated. Here, we demonstrated that the cytosolic carboxyl terminus of OsSWEET11a/Xa13 is required for complementing susceptibility to PXO99 in IRBB13 (xa13/xa13). Interestingly, the C-terminus of ZmXa13, the maize homologue of OsSWEET11a/Xa13, could perfectly substitute for the C-terminus of OsSWEET11a/Xa13. Furthermore, OsSWEET11a/Xa13 interacted with the high-mobility group B1 (OsHMGB1) protein and the small heat shock-like protein OsHsp20L through the same regions in the C-terminus. Consistent with the physical interactions, knockdown or knockout of either OsHMGB1 or OsHsp20L caused an enhanced PXO99-resistant phenotype similar to that of OsSWEET11a/OsXa13. Surprisingly, the plants in which OsHMGB1 or OsHsp20L was repressed developed increased resistance to PXO86, PXO61 and YN24, which carry TALEs targeting OsSWEET14/Xa41 or OsSWEET11a/Xa13. Additionally, OsHsp20L can interact with all six members of clade III OsSWEETs, whereas OsHMGB1 can interact with five other members in addition to OsSWEET12. Overall, we revealed that OsHMGB1 and OsHsp20L mediate conserved BB susceptibility by interacting with clade III OsSWEETs, which are candidates for breeding broad-spectrum disease-resistant rice.

3D bioprinting approaches for spinal cord injury repair.

Regenerative healing of spinal cord injury (SCI) poses an ongoing medical challenge by causing persistent neurological impairment and a significant socioeconomic burden. The complexity of spinal cord tissue presents hurdles to successful regeneration following injury, due to the difficulty of forming a biomimetic structure that faithfully replicates native tissue using conventional tissue engineering scaffolds. 3D bioprinting is a rapidly evolving technology with unmatched potential to create 3D biological tissues with complicated and hierarchical structure and composition. With the addition of biological additives such as cells and biomolecules, 3D bioprinting can fabricate preclinical implants, tissue or organ-like constructs, andin vitromodels through precise control over the deposition of biomaterials and other building blocks. This review highlights the characteristics and advantages of 3D bioprinting for scaffold fabrication to enable SCI repair, including bottom-up manufacturing, mechanical customization, and spatial heterogeneity. This review also critically discusses the impact of various fabrication parameters on the efficacy of spinal cord repair using 3D bioprinted scaffolds, including the choice of printing method, scaffold shape, biomaterials, and biological supplements such as cells and growth factors. High-quality preclinical studies are required to accelerate the translation of 3D bioprinting into clinical practice for spinal cord repair. Meanwhile, other technological advances will continue to improve the regenerative capability of bioprinted scaffolds, such as the incorporation of nanoscale biological particles and the development of 4D printing.

A comparative study of stereo-dependent SSVEP targets and their impact on VR-BCI performance.

Steady-state visual evoked potential brain-computer interfaces (SSVEP-BCI) have attracted significant attention due to their ease of deployment and high performance in terms of information transfer rate (ITR) and accuracy, making them a promising candidate for integration with consumer electronics devices. However, as SSVEP characteristics are directly associated with visual stimulus attributes, the influence of stereoscopic vision on SSVEP as a critical visual attribute has yet to be fully explored. Meanwhile, the promising combination of virtual reality (VR) devices and BCI applications is hampered by the significant disparity between VR environments and traditional 2D displays. This is not only due to the fact that screen-based SSVEP generally operates under static, stable conditions with simple and unvaried visual stimuli but also because conventional luminance-modulated stimuli can quickly induce visual fatigue. This study attempts to address these research gaps by designing SSVEP paradigms with stereo-related attributes and conducting a comparative analysis with the traditional 2D planar paradigm under the same VR environment. This study proposed two new paradigms: the 3D paradigm and the 3D-Blink paradigm. The 3D paradigm induces SSVEP by modulating the luminance of spherical targets, while the 3D-Blink paradigm employs modulation of the spheres' opacity instead. The results of offline 4-object selection experiments showed that the accuracy of 3D and 2D paradigm was 85.67 and 86.17% with canonical correlation analysis (CCA) and 86.17 and 91.73% with filter bank canonical correlation analysis (FBCCA), which is consistent with the reduction in the signal-to-noise ratio (SNR) of SSVEP harmonics for the 3D paradigm observed in the frequency-domain analysis. The 3D-Blink paradigm achieved 75.00% of detection accuracy and 27.02 bits/min of ITR with 0.8 seconds of stimulus time and task-related component analysis (TRCA) algorithm, demonstrating its effectiveness. These findings demonstrate that the 3D and 3D-Blink paradigms supported by VR can achieve improved user comfort and satisfactory performance, while further algorithmic optimization and feature analysis are required for the stereo-related paradigms. In conclusion, this study contributes to a deeper understanding of the impact of binocular stereoscopic vision mechanisms on SSVEP paradigms and promotes the application of SSVEP-BCI in diverse VR environments.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Successful Conservative Treatment of Necrotizing Pneumonia in Pediatric Patients: Two Case Reports.

Objective: Necrotizing pneumonia is a rare and serious complication in pediatric patients, and its treatment often involves the complexity of choosing between surgical intervention and medical management. The disease is difficult to treat because of its devastating characteristics and high mortality rate, especially when considering the risks associated with surgery. The purpose of this report is to present two cases of necrotizing pneumonia in pediatric patients and demonstrate successful conservative management to provide additional insights for clinical decision-making. Case Report: We report two pediatric patients, aged 3 years 7 months and 7 years respectively, who presented with varying degrees of clinical symptoms, including persistent high fever, shortness of breath, and were confirmed to have necrotizing pneumonia after thorough diagnosis and underwent a period of intensive care. Weeks of treatment. Both patients received long-term antibiotic therapy, ventilator support, and analgesia. Conservative management including type of antibiotics, duration of treatment, specific parameters of respiratory support, and analgesic medications is detailed. Conclusion: Our case report highlights that necrotizing pneumonia can be successfully treated with conservative treatment, thus obviating the need for early surgical intervention. These findings are potentially important for guiding clinical practice, suggesting that conservative management can be an effective treatment strategy for necrotizing pneumonia in certain circumstances.

ZIF-8 functionalized S-tapered fiber-optic sensor for polystyrene nanoplastics detection by electrostatic adsorption.

Microplastic (MP) residues in marine have become an increasingly serious environmental pollution issue, and in recent years the detection of MPs in marine started to attract worldwide research interests. Optical-fiber-based environmental sensors have been extensively employed for their several merits such as high sensitivity, pressure resistance, compactness and ease of constructing communication networks. However, fiber-optic refractive index sensors are not specifically developed for distinguishing MPs from other inorganic particles suspended in water. In this paper, an metal-organic framework (MOF) ZIF-8 functionalized S-tapered fiber (STF) sensor is proposed for specific detection of polystyrene nanoplastics (PSNPs) in aqueous environment. ZIF-8 coordination nanoporous polymers with different film thickness were immobilized over the surface of the fabricated STF structure based on self-growth technique and yielding a large surface area over the sensor surface. High sensitivity detection can be achieved by converting the concentration perturbation of PSNPs into evanescent waves over the ZIF-8 functionalized STF surface through the strong electrostatic adsorption effect and π-π stacking, while the fabricated sensor is insensitive to gravels with silica as the primary component in water. It is found that the proposed detector with 18 film layers achieves a sensitivity up to 114.1353nm/%(w/v) for the PSNPs concentration range of 0.01 %(w/v) to 0.08 %(w/v).

Investigation of Imidazolinone Herbicide Resistance Gene with KASP Markers for Japonica/Geng Rice Varieties in the Huanghuaihai Region of China.

Rice is a staple food for more than half of the global population due to its food security and sustainable development. Weeds compete with crops for sunlight and indispensable nutrients, affecting the yield and quality of crops. Breeding herbicide-tolerant rice varieties paired with herbicide application is expected to help with weed control. In this study, 194 Japonica/Geng rice varieties or lines collected from the Huanghuaihai region of China were screened by Kompetitive Allele-Specific PCR (KASP) markers based on four mutation sites within OsALS1 (LOC_Os02g30630), which is the target of imidazolinone (IMI) herbicides. Only the OsALS1627N haplotype was identified in 18 varieties, including the previously reported Jingeng818 (JG818), and its herbicide resistance was validated by treatment with three IMIs. To investigate the origin of the OsALS1627N haplotype in the identified varieties, six codominant PCR-based markers tightly linked with OsALS1 were developed. PCR analysis revealed that the other 17 IMI-tolerant varieties were derived from JG818. We randomly selected three IMI-tolerant varieties for comparative whole-genome resequencing with known receptor parent varieties. Sequence alignment revealed that more loci from JG818 have been introduced into IMI-tolerant varieties. However, all three IMI-tolerant varieties carried clustered third type single nucleotide polymorphism (SNP) sites from unknown parents, indicating that these varieties were not directly derived from JG818, whereas those from different intermediate improved lines were crossed with JG818. Overall, we found that only OsALS1627N from JG818 has been broadly introduced into the Huanghuaihai region of China. Additionally, the 17 identified IMI-tolerant varieties provide alternative opportunities for improving such varieties along with other good traits.

Multifunctional tannic acid-based nanocomposite methacrylated silk fibroin hydrogel with the ability to scavenge reactive oxygen species and reduce inflammation for bone regeneration.

The microenvironment of bone defect site is vital for bone regeneration. Severe bone defect is often accompanied with severe inflammation and elevated generation of reactive oxygen species (ROS) during bone repair. In recent years, the unfriendly local microenvironment has been paid more and more attention. Some bioactive materials with the ability to regulate the microenvironment to promote bone regeneration urgently need to be developed. Here, we develop a multifunctional composite hydrogel composed of photo-responsive methacrylate silk fibroin (SFMA), laponite (LAP) nanocomposite and tannic acid (TA), aiming to endow hydrogel with antioxidant, anti-inflammatory and osteogenic induction ability. Characterization results confirmed that the SFMA-LAP@TA hydrogel could significantly improve the mechanical properties of hydrogel. The ROS-Scavenging ability of the hydrogel enabled bone marrow mesenchymal stem cells (BMSCs) to survive against H2O2-induced oxidative stress. In addition, the SFMA-LAP@TA hydrogel effectively decreased the expression of pro-inflammatory factors in RAW264.7. More importantly, the SFMA-LAP@TA hydrogel could enhance the expression of osteogenic markers of BMSCs under inflammatory condition and greatly promote new bone formation in a critical-sized cranial defect model. Above all, the multifunctional hydrogel could effectively promote bone regeneration in vitro and in vivo by scavenging ROS and reducing inflammation, providing a prospective strategy for bone regeneration.

Multiparametric MRI-based intratumoral and peritumoral radiomics for predicting the pathological differentiation of hepatocellular carcinoma.

PURPOSE: To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. METHODS: A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). RESULTS: Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. CRITICAL RELEVANCE STATEMENT: Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. KEY POINTS: • Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. • The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. • The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation.

Osteoinductive Dental Pulp Stem Cell-Derived Extracellular Vesicle-Loaded Multifunctional Hydrogel for Bone Regeneration.

Stem cell-derived extracellular vesicles (EVs) show great potential for promoting bone tissue regeneration. However, normal EVs (Nor-EVs) have a limited ability to direct tissue-specific regeneration. Therefore, it is necessary to optimize the osteogenic capacity of EV-based systems for repairing extensive bone defects. Herein, we show that hydrogels loaded with osteoinductive dental pulp stem cell-derived EVs (Ost-EVs) enhanced bone tissue remodeling, resulting in a 2.23 ± 0.25-fold increase in the expression of bone morphogenetic protein 2 (BMP2) compared to the hydrogel control group. Moreover, Ost-EVs led to a higher expression of alkaline phosphatase (ALP) (1.88 ± 0.16 of Ost-EVs relative to Nor-EVs) and the formation of orange-red calcium nodules (1.38 ± 0.10 of Ost-EVs relative to Nor-EVs) in vitro. RNA sequencing revealed that Ost-EVs showed significantly high miR-1246 expression. An ideal hydrogel implant should also adhere to surrounding moist tissues. In this study, we were drawn to mussel-inspired adhesive modification, where the hydrogel carrier was crafted from hyaluronic acid (HA) and polyethylene glycol derivatives, showcasing impressive tissue adhesion, self-healing capabilities, and the ability to promote bone growth. The modified HA (mHA) hydrogel was also responsive to environmental stimuli, making it an effective carrier for delivering EVs. In an ectopic osteogenesis animal model, the Ost-EV/hydrogel system effectively alleviated inflammation, accelerated revascularization, and promoted tissue mineralization. We further used a rat femoral condyle defect model to evaluate the in situ osteogenic ability of the Ost-EVs/hydrogel system. Collectively, our results suggest that Ost-EVs combined with biomaterial-based hydrogels hold promising potential for treating bone defects.

Phage P2-71 against multi-drug resistant Proteus mirabilis: isolation, characterization, and non-antibiotic antimicrobial potential.

Proteus mirabilis, a prevalent urinary tract pathogen and formidable biofilm producer, especially in Catheter-Associated Urinary Tract Infection, has seen a worrying rise in multidrug-resistant (MDR) strains. This upsurge calls for innovative approaches in infection control, beyond traditional antibiotics. Our research introduces bacteriophage (phage) therapy as a novel non-antibiotic strategy to combat these drug-resistant infections. We isolated P2-71, a lytic phage derived from canine feces, demonstrating potent activity against MDR P. mirabilis strains. P2-71 showcases a notably brief 10-minute latent period and a significant burst size of 228 particles per infected bacterium, ensuring rapid bacterial clearance. The phage maintains stability over a broad temperature range of 30-50°C and within a pH spectrum of 4-11, highlighting its resilience in various environmental conditions. Our host range assessment solidifies its potential against diverse MDR P. mirabilis strains. Through killing curve analysis, P2-71's effectiveness was validated at various MOI levels against P. mirabilis 37, highlighting its versatility. We extended our research to examine P2-71's stability and bactericidal kinetics in artificial urine, affirming its potential for clinical application. A detailed genomic analysis reveals P2-71's complex genetic makeup, including genes essential for morphogenesis, lysis, and DNA modification, which are crucial for its therapeutic action. This study not only furthers the understanding of phage therapy as a promising non-antibiotic antimicrobial but also underscores its critical role in combating emerging MDR infections in both veterinary and public health contexts.

A nanoparticle reinforced microporous methacrylated silk fibroin hydrogel to promote bone regeneration.

Natural polymer-based hydrogels have been widely applied in bone tissue engineering due to their excellent biocompatibility and outstanding ability of drug encapsulation. However, they have relatively weak mechanical properties and lack bioactivity. Hence, we developed a bioactive nanoparticle composite hydrogel by incorporating LAPONITE®, which is an osteo-inductive inorganic nanoparticle. The incorporation of the nanoparticle significantly enhanced its mechanical properties. In vitro evaluation indicated that the nanocomposite hydrogel could exhibit good biocompatibility. Besides, the nanocomposite hydrogel was proved to have excellent osteogenic ability with up-regulated expression of osteogenic markers such as type I collagen (COL-I), runt-related transcription factor-2 (Runx-2) and osteocalcin (OCN). Furthermore, the in vivo study confirmed that the composite nanocomposite hydrogel could significantly promote new bone formation, providing a prospective strategy for bone tissue regeneration.

Luteolin enhanced antioxidant capability and induced pyroptosis through NF-κB/NLRP3/Caspase-1 in splenic lymphocytes exposure to ammonia.

During feeding process in intensive chicken farms, the prolonged exposure of chickens to elevated level of ammonia leads to substantial economic losses within poultry farming industry. Luteolin (Lut), known as its anti-inflammatory and antioxidant properties, possesses the ability to eliminate free radicals and enhance the activities of antioxidant enzymes, thus rendering it highly esteemed in production. The objective of this study was to examine the effects of Lut on antioxidant and anti-inflammatory responses of chicken splenic lymphocytes exposed to ammonia. In order to achieve this, we have replicated a protective model involving Lut against ammonia exposure in chicken splenic lymphocytes. The findings of the study indicated that Lut mitigated the elevation of lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) induced by ammonia poisoning. Additionally, Lut demonstrated an increase in the expression of antioxidant enzymes, namely superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Furthermore, Lut exhibited a protective effect on cell morphology and ultrastructure following exposure to ammonia. Moreover, Lut exhibited a reduction in the expression of heat shock proteins (HSPs) and inflammatory cytokines, which were found to be highly expressed in splenic lymphocytes after ammonia exposure. Additionally, Lut demonstrated the ability to inhibit the overexpression of pyroptosis-related genes and proteins (NLRP3 and Caspase-1) in splenic lymphocytes following ammonia exposure. Lut exerted an antioxidant effect on lymphocytes, counteracting elevated levels of oxidative stress following exposure to ammonia. Additionally, Lut had the potential to modulate the expression of HSPs, suppressed the inflammatory response subsequent to ammonia exposure, and influenced the expression of NLRP3 and Caspase-1, thereby mitigating pyroptosis induced by ammonia exposure. The exploration of this subject matter can elucidate the protective properties of Lut against NH4Cl-induced damage in chicken splenic lymphocytes, while also offer insights and experimental groundwork for the utilization of natural therapeutics in animal husbandry to prevent and treat ammonia-related conditions.

Prognostic nomogram model for selecting between transarterial chemoembolization plus lenvatinib, with and without PD-1 inhibitor in unresectable hepatocellular carcinoma.

OBJECTIVES: To establish and verify a prognostic nomogram model for selecting in unresectable hepatocellular carcinoma (uHCC) treated by transarterial chemoembolization plus lenvatinib (TACE-L) with or without PD-1 inhibitor. METHODS: Data of 241 uHCC patients who underwent TACE-L (n = 128) and TACE-L plus PD-1 inhibitor (TACE-L-P, n = 113) were retrospectively reviewed. The differences in tumour responses, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) between two groups were compared, and a prognostic nomogram model was established based on independent clinical-radiologic factors and confirmed by Cox regression analysis for predicting PFS and OS. The treatment selection for uHCC patients was stratified by the nomogram score. RESULTS: Compared to TACE-L, TACE-L-P presented prolonged PFS (14.0 vs. 9.0 months, P < .001), longer OS (24.0 vs. 15.0 months, P < .001), and a better overall objective response rate (54.0% vs. 32.8%, P = .001). There was no significant difference between the rate of AEs in the TACE-L-P and the TACE-L (56.64% vs. 46.09%, P = .102) and the rate of grade ≥ 3 AEs (11.50% vs. 9.38%, P = .588), respectively. The nomogram model presented good discrimination, with a C-index of 0.790 for predicting PFS and 0.749 for predicting OS. Patients who underwent TACE-L and obtained a nomogram score >9 demonstrated improved 2-year PFS when transferred to TACE-L-P, and those with a nomogram ≤25 had better 2-year OS when transferred to TACE-L-P. CONCLUSIONS: TACE-L-P showed significant improvements in efficiency and safety for uHCC patients compared with TACE-L. The nomogram was useful for stratifying treatment decisions and selecting a suitable population for uHCC patients. ADVANCES IN KNOWLEDGE: Prognostic nomogram model is of great value in predicting individualized survival benefits for uHCC patients after TACE-L or/and TACE-L-P. And the nomogram was helpful for selection between TACE-L-P and TACE-L among uHCC patients.

Combustion Enhancement of Gel Propellant Containing High Concentration Aluminum Particles Based on Carbon Synergistic Effect.

The addition of aluminum particles to gel propellants can improve combustion performance. However, the agglomeration of aluminum during the combustion process can result in a series of negative effects. In this paper, the aluminum agglomeration inhibition method of gel propellant based on carbon synergistic effect is proposed. Carbon particles exhibit excellent combustion properties, and the gaseous product CO2 generated during combustion can mitigate the agglomeration of aluminum. The research demonstrates that incorporating carbon particles into aluminum-containing gel effectively reduces the incomplete combustion of aluminum particles and increases the volumetric calorific value of the gel. When the mass fraction of carbon is 5 wt%, the volume calorific value of the gel reaches the highest. Meanwhile, the rheological experiments show that the addition of carbon particles can improve the shear-thinning properties of the gel, which is beneficial to the atomization and combustion processes of the gel.

Protective effects of an alcoholic extract of Kaempferia galanga L. rhizome on ethanol-induced gastric ulcer in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Kaempferia galanga L., a medicinal and edible Plant, was widely distributed in many Asian and African counties. It has been traditionally used to treat gastroenteritis, hypertension, rheumatism and asthma. However, there is a lack of modern pharmacology studies regarding its anti-gastric ulcer activity. AIM OF THE STUDY: The objective of this study is to investigate the protective effects of an extract from K. galanga L. rhizome (Kge) and its active components kaempferol and luteolin on ethanol-induced gastric ulcer. MATERIALS AND METHODS: The kge was prepared by ultrasonic-assisted extraction, and the contents of kaempferol and luteolin were determined by HPLC. The mice were randomly divided into seven groups: blank control (0.5 % CMC-Na; 0.1 mL/10 g), untreatment (0.5 % CMC-Na; 0.1 mL/10 g), Kge (100, 200 and 400 mg/kg), kaempferol (100 mg/kg) and luteolin (100 mg/kg) groups. The mice were treated intragastrically once daily for 7 days. At 1 h post the last administration, the mice in all groups except the blank control group were intragastrically administrated with anhydrous alcohol (0.1 mL/10 g) once to induce gastric ulcer. Then, fasting was continued for 1 h, followed by sample collection for evaluation by enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction assay. RESULTS: The contents of kaempferol and luteolin in Kge were determined as 3713 µg/g and 2510 µg/g, respectively. Alcohol induced severely damages with edema, inflammatory cell infiltration and bleeding, and the ulcer index was 17.63 %. After pre-treatment with Kge (100, 200 and 400 mg/kg), kaempferol and luteolin, the pathological lesions were obviously alleviated and ulcer indices were reduced to 13.42 %, 11.65 %, 6.54 %, 3.58 % and 3.85 %, respectively. In untreated group, the contents of Ca2+, myeloperoxidase, malondialdehyde, NO, cyclic adenosine monophosphate and histamine were significantly increased, while the contents of hexosamine, superoxide dismutase, glutathione peroxidase, and prostaglandin E2 were significantly decreased; the transcriptional levels of IL-1α, IL-1ß, IL-6, calcitonin gene related peptide, substance P, M3 muscarinic acetylcholine receptor, histamine H2 receptor, cholecystokinin 2 receptor and H+/K+ ATPase were significantly increased when compared with the blank control group. After pre-treatment, all of these changes were alleviated, even returned to normal levels. Kge exhibited anti-gastric ulcer activity and the high dose of Kge (400 mg/kg) exhibited comparable activity to that of kaempferol and luteolin. CONCLUSION: The study showed that K. galanga L., kaempferol, and luteolin have protective effects against ethanol-induced gastric ulcers. This is achieved by regulating the mucosal barrier, oxidative stress, and gastric regulatory mediators, as well as inhibiting the TRPV1 signaling pathway and gastric acid secretion, ultimately reducing the gastric ulcer index.